Nuclear factor kappa B (NF-κB) signaling pathway components (NF-κB signaling pathway)

The Nuclear factor kappa B (NF-κB) signaling pathway is a critical mediator of the cellular response to external stimuli, including cytokines, radiation, and pathogens. It comprises a family of transcription factors—p50, p52, p65 (RelA), RelB, and c-Rel—that regulate the expression of genes involved in inflammation, immune function, cell proliferation, and apoptosis (Zhang et al., 2017). In resting cells, NF-κB dimers are held in the cytoplasm by inhibitor of κB (IκB) proteins; activation typically involves the IκB kinase (IKK) complex, which phosphorylates IκB, marking it for proteasomal degradation (Oeckinghaus & Ghosh, 2009). This release allows NF-κB to enter the nucleus and activate target genes. Aberrant NF-κB activity is a hallmark of many human diseases, particularly chronic inflammatory conditions like rheumatoid arthritis and various malignancies where it drives cell survival and chemoresistance (Taniguchi & Karin, 2018). Therapeutic strategies targeting this pathway include proteasome inhibitors like bortezomib, which prevent IκB degradation, and corticosteroids that upregulate IκB expression, though broad inhibition often faces challenges due to the pathway's essential role in normal immunity (Baud & Karin, 2009).

Other names

NF-kappaB signalingREL/NF-kappaB pathwayNuclear factor-kappa B pathwayNFKB pathwayNF-kappaB signaling cascade

Drugs targeting this pathway primarily act by inhibiting the 26S proteasome to prevent the degradation of IκB proteins, inhibiting the IκB kinase (IKK) complex to prevent IκB phosphorylation, or inducing the expression of IκB to sequester NF-κB in the cytoplasm.